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N Sanz

Publications and source records attributed to N Sanz.

At least 37 records · Page 2Linked to original sources
PubMed1997

Malic enzyme and glucose 6-phosphate dehydrogenase gene expression increases in rat liver cirrhogenesis.

The cirrhogenic ability of thioacetamide has been used to induce a model of chronic generalized liver disease that resembles the preneoplastic state of human fibrosis. Malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PDH) are two cytosolic NADPH-generating enzymes; their activities significantly increased in liver when macronodular cirrhosis was induced by long-term thioacetamide administration to rats. The progressive increase in G6PDH and ME activities during the cirrhogenic process is parallel to the induction in gene expression of both enzymes detected by the increase in their mRNAs. These data indicate that NADPH-consuming mechanisms such as the microsomal oxidizing system and the maintenance of the cell redox state could be involved. A relationship between the extent of G6PD and ME gene expression and oxidative stress generated by the oxidative metabolism of thioacetamide is proposed as the hepatic concentration of malondialdehyde, a metabolite derived from lipid peroxidation, underwent a progressive and significant enhancement during thioacetamide-induced cirrhogenesis. These results led us to suggest that the enhanced activities of G6PDH and ME might be related to microsomal mechanisms of detoxification as well as to the maintenance of the cellular redox state. Furthermore, the noticeable increase in the hepatocyte population involved in DNA replication parallel to G6PDH activity suggests that G6PDH, through ribose-5-phosphate, might also be involved in the processes of DNA synthesis and repair.

Animals↗
PubMed1997

Involvement of nitric oxide synthesis in hepatic perturbations induced in rats by a necrogenic dose of thioacetamide.

1. The biological actions of nitric oxide (NO), a highly diffusible and short-lived radical, range from signal transduction to cytotoxicity. The present study investigated whether NO is released in the course of liver necrosis and regeneration induced by a single necrogenic dose of thioacetamide (6.6 mmol kg-1 body wt) to rats. Samples of liver were obtained at 0, 3, 12, 24, 48, 72 and 96 h after thioacetamide administration. 2. Inducible nitric oxide synthase (iNOS) activity was determined in purified liver homogenates and a sharp 6 fold increase (P < 0.001) in iNOS activity was recorded at 48 h of intoxication, followed by a slight but progressive increase at 72 and 96 h. Changes in the expression of iNOS, as detected by its mRNA levels, were parallel to the NOS enzyme activity. Hepatocyte NO synthesis showed a progressive increase at 24, 48 and 72 h, to 8 (P < 0.001), 13 (P < 0.001) and 13 (P < 0.001) times the initial values, respectively. 3. In isolated Kupffer cells, where initial NO release was ten fold higher than in hepatocytes, a progressive increase was detected from 48 h which reached two fold of initial at 72 h of intoxication (192%; P < 0.001). Hepatic cyclic GMP concentration did not change significantly. However, mitochondrial aconitase activity decreased markedly at 12 and 24 h of intoxication showing a sharp increase towards normal values at 48 h which was maintained at 72 and 96 h. 4. As protein kinase C (PKC) is one of the likely candidates to mediate iNOS expression, translocation (activation) of PKC was assayed in hepatocytes, and a significant two fold increase (P < 0.001) between 48 and 96 h after thioacetamide intoxication was observed. When peritoneal macrophages from control rats were incubated with serum from thioacetamide-treated rats, a sharp increase in NO release was detected with serum obtained at 48 h, reaching at 96 h a value four fold (P < 0.001) that of the control. 5. These results suggest that iNOS activity and NO release play a role in the pathophysiological mechanisms that trigger post-necrotic hepatocellular regeneration following thioacetamide administration.

Aconitate Hydratase↗
PubMed1997

Rhabdomyosarcoma of the biliary tree.

Rhabdomyosarcoma (RMS) of the biliary tree is a rare tumor in children that has a very poor prognosis. Preoperatively, it is often mistaken for a choledochal cyst. We report a case of RMS of the biliary tree in a 4-year-old girl who presented with abdominal pain and obstructive jaundice. The RMS was diagnosed at laparotomy; excision was not possible due to its size and localization. Chemotherapy achieved complete regression of the tumor observed at second-look surgery. Preoperative chemotherapy can now avoid mutilating surgical procedures and improve survival.

Anastomosis, Roux-en-Y↗
PubMed1996

Changes in glucose-6-phosphate dehydrogenase and malic enzyme gene expression in acute hepatic injury induced by thioacetamide.

NADPH-generating enzymes, glucose-6-phosphate dehydrogenase (G6PDH), and malic enzyme (ME) were studied in rat liver when necrosis and regeneration were induced by a single sublethal dose of thioacetamide (6.6 mmol/kg). Both enzyme activities decreased sharply at 12-24 hr of treatment and increased thereafter. These biphasic changes are related to the sequential processes of liver injury and hepatocellular regeneration. Expression of mRNA for G6PDH decreased at 12 hr following thioacetamide injection and increased during liver regeneration, reaching its highest levels of expression at 48 hr (247% of the control), parallel to the peak of DNA synthesis. Expression of ME decreased at 12-24 hr and increased during the postnecrotic regenerating process, reaching only half of the control value at 96 hr. A relationship between mRNA G6PDH gene expression, oxidative stress (detected by the GSH/GSSG ratio and malondialdehyde (MDA) concentration), and DNA synthesis is proposed.

Animals↗
PubMed1996

Variations of hepatic antioxidant systems and DNA ploidy in rats aged 2 to 8 months.

Oxygen-reactive species are by-products of biological redox reactions and are involved in the development and aging processes. In order to test whether the time-dependent changes in the hepatic antioxidant defense are related to changes in DNA ploidy, we studied in rats, aged 2-8 months, the enzymes and metabolites related to the primary cell defense against oxidative stress, as well as the distribution of DNA into the cell cycle phases. Catalase and glutathione peroxidase, together with glutathione reductase and mitochondrial superoxide dismutase, underwent progressive and significant time course increases. Although no temporal changes were observed in the concentration of protein thiol groups and malondialdehyde in rats in the same age period, glutathione redox state, detected by the GSH/GSSG ratio decreased significantly to 41% (P<0.001) of the initial value. DNA content was assayed by flow cytometry in isolated hepatocytes, and changes in DNA ploidy and distribution in the cell cycle phases were determined. A sharp decrease in diploid population from rats aged 1-8 months (92.9% --> 11.1%) and a pronounced increase in hepatocyte polyploid populations in the same age period (2.6% --> 87.3%) were observed. However, liver cell population involved in S phase (DNA synthesis) was unchanged. These results indicate that the cell defense mechanisms against oxygen toxicity increased in liver of rats from 2-8 months in order to suppress the oxidative imbalance. During the 6-month period of a rat's life (2-8 months), the significant alterations of GSH/GSSG ratio to a more oxidative state have no influence on the proliferating capacity of the cells.

Aging↗
PubMed1996

Intracellular calcium concentration impairment in hepatocytes from thioacetamide-treated rats. Implications for the activity of Ca(2+)-dependent enzymes.

METHODS/RESULTS: Thioacetamide induced a severe perivenous necrosis followed by a hepatocellular regenerative response, when administered in a single dose of 6.6 mmol/kg to rats. As (Ca2+)i plays an important role in both toxic cell killing and cell proliferation, the disturbances in the basal cytosolic calcium as well as the levels of Ca2+ sequestered in the endoplasmic reticulum were determined in hepatocytes isolated at 0, 12, 24, 48 and 72 h after thioacetamide administration. The basal Ca2+ increased progressively, reaching a maximum at 24 h of the intoxication (205%, p < 0.001), while the microsomal sequestered Ca2+ decreased at 24 h to 16% (p < 0.001) when compared with untreated controls. Changes in the activity of glycogen phosphorylase alpha paralleled those of basal free calcium and showed the maximum value also at 24 h (291%; p < 0.001). Moreover, there was a close association in time between the basal concentration of Ca2+ and the inhibition of microsomal Ca(2+)-dependent ATPase activity. CONCLUSIONS: The significant decrease in the levels of GSH and protein thiols indicates that oxidative stress is involved in thioacetamide-induced cell injury, but these decreases did not precede changes in cytosolic Ca2+ level. In the sequence of events leading to hepatic cell injury and regeneration, thioacetamide mobilized hepatic (Ca2+)i via inhibition of microsomal Ca(2+)-ATPase which may have activated Ca(2+)-dependent mechanisms involved both in cell death and in acute mitogen response.

Animals↗
PubMed1996

[Intussusception: barium vs. pneumatic reduction].

At the Hospital Niño Jesús air pressure enema has recently replaced the use of barium as treatment of choice in the reduction of intussusception. The purpose of this study was to review the air enema reductions done from June 1992 to February 1994 in 137 patients (group II) and to compare them with a previous series of 153 patients that underwent barium reduction treatment (group I). The groups were similar with regard to sex, age and presentins symptoms as well as clinical signs. Successful reduction was achieved in 131 patients (85.6%) out of 146 attempts treated with barium enema and in 124 patients (90.5%) out of 134 attempts treated with air enema. Among the unsuccessful reduction cases, operation was performed in 22 cases in group I and in 13 cases of group II. In the group I there were two perforations during the reduction attempt, while in group II we did not have any with the air enema. There were two recurrent intussusceptions following barium enema reduction and nine following air enema reduction in the first 48 hours. Patients treated with air enema stayed less days at hospital (1,6 days) than those treated with barium (3 days). We believe that the air enema treatment is easy to perform, is lower in cost and presents less morbility, and that it should be considered as the treatment of choice in the initial management of intussusception.

Barium↗
PubMed1996

[The colonic atresia: an uncommon cause of neonatal intestinal obstruction].

The intestinal atresia is a common cause of neonatal bowel obstruction, but the colonic atresia is an uncommon cause of neonatal intestinal obstruction. We present a newborn with congenital colon atresia who underwent laparotomy, revealing a colonic atresia type III. We recommend resection of the dilated proximal colon with primary anastomosis end to end if the patient is not perforated or in bad general conditions.

Anastomosis, Surgical↗
PubMed1995

Relationship between antioxidant systems, intracellular thiols and DNA ploidy in liver of rats during experimental cirrhogenesis.

Hyperplastic nodular cirrhosis was induced in rats by long-term (6 month) i.p. administration of thioacetamide at doses of 2.66 mmol/kg body wt, three times per week. The survival rate of animals at the end of the treatment was 90%. To follow the temporal changes samples at 0, 7, 15, 30, 45, 60, 90, 150 and 180 days from rats during thioacetamide intoxication and from chronological controls were obtained. The cirrhogenic ability of this treatment was assessed on the basis of morphological changes: the development of macronodular cirrhosis and the appearance of fibrous septa of collagen through portal spaces. Parameters of liver injury and cholestasis were obtained by assaying the serum activities of isocitrate dehydrogenase and gamma-glutamyltransferase. Enzymes and metabolites related to glutathione redox systems, as well as other antioxidant enzymes, were tested. Catalase and glutathione peroxidase, the two enzymes involved in the elimination of peroxides, and glutathione reductase decreased significantly at the end of the 6 months of intoxication, while Cu-Zn and Mn superoxide dismutases increased progressively during the long-term thioacetamide treatment. Protein thiol levels profile showed a biphasic change increasing from the 7th day and were insensitive to the 30% depletion of intracellular glutathione (GSH). To study the relationship of the intracellular thiols on the mechanisms of cell proliferation and differentiation during the cirrhogenic process, DNA content was assayed by flow cytometry in isolated hepatocytes, and DNA ploidy and distribution between G0-G1, S and G2 + M phases were determined. Remarkable changes in relation to a sharp increase in diploid population from 7 to 180 days (24.5%-->85.5%), a pronounced decrease in polyploid populations (tetraploid+octoploid) in the same period (73.7%-->12.3%), and elevations in the populations in S phase (S1 + S2) were observed in thioacetamide-treated rats. The results obtained indicate that hepatocytes isolated from thioacetamide-treated rats showed a marked tendency to diploidy, an enhancement in DNA replication parallel to the hepatic content of protein sulphydryl groups and a significant decline in antioxidant enzyme activities. The increase in protein thiols was independent of GSH level and of the thiol redox state.

Animals↗
PubMed1994

Cocaine-induced liver injury in mice elicits specific changes in DNA ploidy and induces programmed death of hepatocytes.

Liver injury was induced by a single dose (60 mg/kg) of cocaine in male albino Swiss mice untreated or pretreated with phenobarbital (in drinking water 1 gm/L), for 5 days before cocaine administration. One parameter of liver injury, serum isocitrate dehydrogenase activity, showed sharp increases at 24 hr of cocaine treatment; we also noted decrease hepatic levels of ATP, GSH, cytochrome P-450 and NADPH/NADP+ ratio and increases in malondialdehyde concentration. Histopathological study of liver slices showed perivenous and periportal necrosis induced by cocaine in untreated mice and mice pretreated with phenobarbital, respectively. A regenerative postnecrotic response, which peaked at 48 hr, was demonstrated by the appearance of mitotic cells. Mitotic index analysis showed that proliferative cells appear to be unevenly distributed in the hepatic acinus and were mainly located in the vicinity of the damaged acinar region. Genomic DNA ploidy and the distribution of DNA in the phases of the cell cycle were studied in nuclei of isolated hepatocytes. At 12 hr of cocaine administration, both in untreated and phenobarbital-pretreated mice, the following changes were observed: a sharp decrease in tetraploid (4N) cells (40% to 17% and 25% to 6%, respectively) and octoploid (8N) cells (5% to 2% and 2% to 1%, respectively), together with the appearance of a hypodiploid population (13% and 31%, respectively). Hypodiploid population was characterized as apoptotic cells by detection of DNA fragmentation in agarose gel. These results suggest that a significant percentage of cell death induced by cocaine occurs by means of the apoptosis death program. Comparison of the initial values of DNA ploidy with those obtained at 7 days of cocaine administration showed remarkable increases in polyploid populations (4N and 8N) and a decrease in diploid cells (2N), indicating that the process of differentiation occurs when liver restores its functionality.

Adenosine Triphosphate↗
PubMed1994

[Intestinal pseudo-obstruction secondary to systemic neuropathies and myopathies].

The term intestinal pseudo-obstruction, is applied to a group of clinical disorders in which there are obstructive symptoms, in the absence of a mechanical agent, secondary to a disorder of intestinal motility. In this report, we show manometric studies done in four patients, with acute intestinal pseudo-obstructions, secondary to von Recklinghausen's neurofibromatosis (VRNF), in two patients, and in one patient with Duchenne's muscular dystrophy (DMD) and in another with Werdnig-Hoffmann's disease (WHD). We studied 24 hours antroduodenal motility, specially during phase 3 of the migratory motor complex (CMM), which showed a neuropathic disorder in one case of von Recklinghausen's disease and a myopathic disorder in patients with Duchenne's muscular dystrophy and Werdnig-Hoffmann's disease. We analysed results and conclusions and specially the kinetic action of erythromycin.

Adolescent↗
PubMed1994

[Middle lobe syndrome].

Middle lobe syndrome (MLS) or atelectasis syndrome can affect any pulmonary lobe but occurs more frequently in the right middle lobe. Only 15 per cent of the reported cases are children. We report two cases of MLS in two boys of 4 and 12 years of age who were referred to our institution because they had suffered from recurrent pneumonies of the right middle lobe for ten months and six years respectively. We performed chest radiographs, computed tomography scanning, ventilation-perfusion scintigraphy and flexible bronchoscopy. The evolution in both cases to an atelectasic middle lobe with pulmonary shrinkage and lack of perfusion was the indication to lobectomy. Histological examination showed a bronchial obstructive process in the young patient and a chronic non specific inflammation of the pulmonary parenchyma in both. The resection brought about a cure. The identification of MLS is usually a late diagnosis. Thus, if atelectasis persists after an adequate medical therapy, resection of the lobe is indicated.

Child↗
PubMed1992

Hypertrophic cardiomyopathy in mucopolysaccharidoses: regression after bone marrow transplantation.

Mucopolysaccharide storage disease (MPS) presents clinically with a broad spectrum of abnormalities, among which cardiovascular involvement has been described. The echocardiographic findings have recently been reported for the various types of MPS. Among these, asymmetric septal hypertrophy (ASH) has been documented. We present a case of a 9-year-old girl suffering from type I MPS, atypical variant, with echocardiographic signs of ASH. She was given a bone marrow transplant after which the hypertrophic cardiomyopathy regressed.

Bone Marrow Transplantation↗
PubMed1992

[Asplenia syndrome with duodenal stenosis].

We report a patient with asplenia syndrome. To our knowledge this is the first case described of asplenia syndrome with duodenal stenosis and no heart anomalies. An other important finding has been the absence of vomiting in her symptomatology.

Child↗
PubMed1989

Noninvasive assessment of cardiomyopathy in normotensive diabetic patients between 20 and 50 years old.

PURPOSE: To further the understanding of diabetic heart disease, we tested the hypothesis that an asymptomatic group of normotensive diabetic patients between 20 and 50 years old had a restrictive cardiomyopathy independent of clinically significant coronary artery disease. PATIENTS AND METHODS: Quantitative two-dimensional echocardiography and stress myocardial perfusion scintigraphy were performed to detect and characterize the cardiac abnormalities in this study group comprising 88 patients with rigorously classified diabetes and 65 volunteer control subjects. RESULTS: Diabetic patients were shown to have a mildly reduced left ventricular end-diastolic volume index: 50.1 +/- 8.2 and 52.1 +/- 14.7 mL/m2 for patients with type I and type II diabetes, respectively, versus 58.9 +/- 11.7 mL/m2 for control subjects. The left ventricular diastolic filling was also impaired in diabetic patients as reflected by a lower atrial emptying index: 0.73 +/- 0.24 and 0.76 +/- 0.3 for type I and type II diabetics, respectively, compared with 1.14 +/- 0.24 for control subjects. Exercise tolerance was normal in subjects with type I diabetes and slightly reduced in subjects with type II diabetes. Only one patient developed regional ischemia on thallium exercise testing. CONCLUSION: Using a comprehensive, noninvasive approach, we have shown that asymptomatic normotensive patients with type I or type II diabetes who were between 20 and 50 years old had a restrictive cardiomyopathy characterized by mildly reduced left ventricular end-diastolic volume and altered left ventricular compliance independent of critical coronary artery disease.

Adult↗
PubMed1989

Insulin-receptor and apolipoprotein genes contribute to development of NIDDM in Chinese Americans.

The frequencies of restriction-fragment-length polymorphism (RFLP) alleles as well as RFLP haplotypes at six genetic loci responsible for carbohydrate and lipid metabolism [insulin/insulin-like growth factor II complex, insulin receptor (INSR), HepG2/erythrocyte-type glucose transporter, apolipoprotein A-II, apolipoprotein B (APOB), and the apolipoprotein A-I/C-III/A-IV cluster (APOA1/C3/A4)] were compared between nondiabetic and diabetic Chinese Americans. The disease-association data suggest that genetic variation at the INSR, APOB, and APOA1/C3/A4 loci contributes to the development of non-insulin-dependent diabetes mellitus (NIDDM). The analysis of the INSR locus revealed "protective" haplotypes, and it may be possible to use two of the INSR haplotypes as genetic markers to identify individuals having a very low probability of developing NIDDM regardless of the presence of other genes conferring susceptibility to this disorder. The APOB and APOA1/C3/A4 loci appear to contribute to the development of NIDDM in individuals who are of lean/normal weight and overweight, respectively. The APOA1/C3/A4 locus may account for approximately 8% of the difference between baseline and total possible risk of NIDDM in overweight individuals.

Adult↗
PubMed1987

The molecular genetics of diabetes mellitus.

Diabetes mellitus is a clinically heterogeneous disorder which is characterized by hyperglycaemia due to an absolute or relative deficiency of insulin. Both genetic and non-genetic factors contribute to its development and, as such, it represents a multifactorial disorder. In addition, it may also be, in some instances, a polygenic disorder resulting from the cumulative effects of several genes with or without environmental factors. Serological and/or DNA markers for genes that confer susceptibility to the insulin-dependent form of the disorder (IDDM; type 1) have been identified in the HLA-D region of chromosome 6 and near the insulin gene on chromosome 11. Patients with non-insulin-dependent diabetes mellitus (NIDDM; type 2) make up a more heterogeneous group than those with IDDM and it is likely that in these patients similar clinical phenotypes may be produced by different genetic defects. The synthesis of either an abnormal insulin/proinsulin molecule or an abnormal insulin receptor can confer susceptibility to NIDDM. The genes encoding insulin and the insulin receptor are on chromosomes 11 and 19, respectively. In addition, studies of restriction fragment length polymorphism and disease associations suggest that two other genes may contribute to the development of NIDDM on chromosome 11, one near the insulin gene on the short arm of this chromosome and the other near the apolipoprotein A-I gene on the long arm. None of the susceptibility genes that have been identified to date causes diabetes in the absence of other genetic or non-genetic contributing factors, which is consistent with a multifactorial or polygenic origin for this disorder.

Alleles↗